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1.
The objectives were to document the pharmacokinetics of intravenous, enteric‐coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric‐coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fasted state (ECO‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fed state (ECO‐Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL‐Fasted). Plasma omeprazole concentrations were determined by UHPLC‐MS. Bioavailability was higher (P = 0.038) in the ECO‐Fasted group (21.5 [9.0–27.7]%) than the PL‐Fasted group (10.1 [7.7–13.3]%). Similarly, AUC0‐∞ was higher in the ECO‐Fasted group than the PL‐Fasted group (P = 0.027). No significant differences were present between the ECO‐Fasted and ECO‐Fed groups with regards to bioavailability, Cmax, Tmax or AUC0‐∞. When the half‐life data from the oral formulations was pooled, it was longer than that observed in the IV‐Fasted group (100 [73–118] min) and 35 [34‐39] min, respectively; P < 0.0001). Bioavailability of enteric‐coated omeprazole was higher than previously reported and feeding had minimal impact. Bioavailability of plain omeprazole was approximately half that of enteric‐coated omeprazole. The longer half‐life observed following oral administration was consistent with the flip‐flop effect and has not previously been described for omeprazole in the horse.  相似文献   

2.
A new formulation of omeprazole in gastro‐resistant granules was tested with regard to its pharmacokinetics and tolerability. Twenty‐four horses were randomly divided into three groups (8 horses/group) and treated, according a parallel study design, as follows: Group A untreated (control group), Group B received 4 mg/kg of omeprazole, and Group C received 12 mg/kg of omeprazole, both of which were treated orally once a day for 90 days. Blood samples, taken from Group B subjects during the 1st and the 29th day of treatment at pre‐established time points, were used to determine the concentration–time curves of omeprazole. The treatments were found to be safe and well tolerated by the horses. The serum hematological and biochemical values were within reference ranges for the entire observational time. No accumulation of the drug was found after 29 days of treatment. Lower Cmax and AUCs were obtained at the 29th day of treatment.  相似文献   

3.
The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2‐amino‐5‐thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high‐performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125–2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration–time curves (AUC) of cefquinome showed a dose‐dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half‐life values (2.30–2.41 h), the mean residence time (1.77–2.25 h), the systemic clearance (158–241 mL/h/kg), and the volume of distribution at steady‐state (355–431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUCsynovial fluid/AUCplasma ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12‐h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.  相似文献   

4.
Minocycline is commonly used to treat bacterial and rickettsial infections in adult horses but limited information exists regarding the impact of feeding on its oral bioavailability. This study's objective was to compare the pharmacokinetics of minocycline after administration of a single oral dose in horses with feed withheld and with feed provided at the time of drug administration. Six healthy adult horses were administered intravenous (2.2 mg/kg) and oral minocycline (4 mg/kg) with access to hay at the time of oral drug administration (fed) and with access to hay delayed for 2 hr after oral drug administration (fasted), with a 7‐day washout between treatments. Plasma concentration versus time data was analyzed based on noncompartmental pharmacokinetics. Mean ± SD bioavailability (fasted: 38.6% ± 4.6; fed: 15.7% ± 2.3) and Cmax (fasted: 1.343 ± 0.418 μg/ml; fed: 0.281 ± 0.157 μg/ml) were greater in fasted horses compared to fed horses (p < .05 both). Median (range) Tmax (hr) in fasted horses was 2.0 (1.5–3.5) and in fed horses was 5.0 (1.0–8.0) and was not significantly different between groups. Overnight fasting and delaying feeding hay 2 hr after oral minocycline administration improve drug bioavailability and thus plasma concentrations.  相似文献   

5.
Devil's claw is used for the treatment of inflammatory symptoms and degenerative disorders in horses since many years, but without the substantive pharmacokinetic data. The pharmacokinetic parameters of harpagoside, the main active constituent of Harpagophytum procumbens DC ex Meisn., were evaluated in equine plasma after administration of Harpagophytum extract FB 8858 in an open, single‐dose, two‐treatment, two‐period, randomized cross‐over design. Six horses received a single dose of Harpagophytum extract, corresponding to 5 mg/kg BM harpagoside, and after 7 days washout period, 10 mg/kg BM harpagoside via nasogastric tube. Plasma samples at certain time points (before and 0–24 hr after administration) were collected, cleaned up by solid‐phase extraction, and harpagoside concentrations were determined by LC‐MS/MS using apigenin‐7‐glucoside as internal standard. Plasma concentration‐time data and relevant parameters were described by noncompartmental model through PKSolver software. Harpagoside could be detected up to 9 hr after administration. Cmax was found at 25.59 and 55.46 ng/ml, t1/2 at 2.53 and 2.32 hr, respectively, and tmax at 1 hr in both trials. AUC0–inf was 70.46 and 117.85 ng hr ml?1, respectively. A proportional relationship between dose, Cmax and AUC was observed. Distribution (Vz/F) was 259.04 and 283.83 L/kg and clearance (CL/F) 70.96 and 84.86 L hr?1 kg?1, respectively. Treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects.  相似文献   

6.
Eight weanling Standardbred horses were used to evaluate the effects on growth and plasma glucose of two differently processed diets with identical ingredients fed at a rate of 3% of body weight, as fed, daily. The daily ration was divided into two equal feedings at 7:00 am and 7:00 pm. The hay and grain diet (diet HG) consisted of 50% alfalfa hay cubes and 50% of a commercial growing horse texturized grain mix fed as is, without any further processing, with each part fed in separate containers. The completely pelleted diet (diet P) consisted of the same proportions of the hay cubes and grain mix that was ground, pelleted, and fed in a single container. Two groups of four horses were fed either diet P or diet HG for two 21-day periods such that each horse consumed each diet for 21 days. On the last day of each feeding period, 7-mL blood samples were drawn into heparinized evacuated blood tubes for determination of plasma glucose concentration. Blood samples were drawn 30 minutes before the afternoon feeding, immediately before, and every 30 minutes thereafter for 5 hours. Analysis of variance found greater (P = .027) average daily gain for horses fed diet P versus diet HG. A nonsignificant difference was seen in feed efficiency (P = .057) for horses fed diet P versus diet HG. Plasma glucose changes were compared across treatments using area under the curve analysis. No difference (P > .05) was found in the postprandial plasma glucose changes between diet treatments.  相似文献   

7.
The use of anti‐ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti‐ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half‐life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection.  相似文献   

8.
The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α‐hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one‐compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0–∞) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1–12 h). Alpha‐hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.  相似文献   

9.
A biological assay was carried out to evaluate the impact of dietary tryptophan (TRP) in aflatoxin B1‐contaminated diets (AFB1‐D) on performance, blood parameters, immunity, meat quality and microbial populations of intestine in Japanese quails. Six experimental diets were formulated to include two levels of dietary TRP; 2.9 (moderate high: MH‐TRP) and 4.9 g/kg (excess: Ex‐TRP); and three levels of AFB1 (0.0, 2.5, and 5.0 mg/kg). Each experimental diet was fed to the one of the six groups of birds from 7 to 35 days of age in a completely randomized design with 2 × 3 factorial arrangement. Decrease in feed intake, body weight gain and gain:feed in birds fed 5.0 mg/kg AFB1‐D was restored to the control level by 4.9 g TRP/kg of the diet. The hepatic enzymes in blood were elevated in quails fed on AFB1‐D but attenuated by 4.9 g TRP/kg of the diet (Ex‐TRP; p ≤ .01). High serum uric acid in birds challenged with AFB1 significantly decreased by Ex‐TRP (p ≤ .01). The skin thickness to 2,4‐dinitro‐1‐chlorobenzene challenge suppressed by AFB1 but increased by Ex‐TRP diet (p ≤ .02). The AFB1 increased the malondialdehyde in meat, whereas TRP efficiently diminished malondialdehyde production (p ≤ .01). The greatest drip loss and pH in meat were observed in the birds fed 5.0 mg/kg AFB1‐D but Ex‐TRP augmented the adverse effects of AFB1 (p ≤ .01). The Ex‐TRP reduced the total microbial and Escherichia coli counts (p ≤ .01). The adverse effect of AFB1 on ileal Lactic acid bacteria was completely prevented by Ex‐TRP (p ≤ .03). This study showed that tryptophan supplementation could be considered as a powerful nutritional tool to ameliorate the adverse effects of AFB1 in growing quails.  相似文献   

10.
The pharmacokinetics of dantrolene and its active metabolite, 5‐hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5‐hydroxydantrolene on activated whole‐blood gene expression of the cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (Cmax) was 0.43 μg/mL, terminal half‐life (t1/2) was 1.26 h, and area under the time–concentration curve (AUC) was 3.87 μg·h/mL. For the 10 mg/kg dose, Cmax was 0.65 μg/mL, t1/2 was 1.21 h, and AUC was 5.94 μg·h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t1/2, for example, ranged from 0.43 to 6.93 h, Cmax ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole‐blood expression of IL‐2 and IFN‐γ as measured by qRT‐PCR was markedly suppressed following exposure to very high concentrations (30 and 50 μg/mL, respectively) of both dantrolene and 5‐hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing.  相似文献   

11.
Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV‐1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV‐1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in six adult horses in a randomized cross‐over design. Ganciclovir sodium was administered intravenously as a slow bolus at a dose of 2.5 mg/kg, and valganciclovir was administered orally at a dose of 1800 mg per horse. Intravenously administered ganciclovir disposition was best described by a three‐compartment model with a prolonged terminal half‐life of 72 ± 9 h. Following the oral administration of valganciclovir, the mean observed maximum serum ganciclovir concentration was 0.58 ± 0.37 μg/mL, and bioavailability of ganciclovir from oral valganciclovir was 41 ± 20%. Superposition predicted that oral dosing of 1800‐mg valganciclovir two times daily would fail to produce and maintain effective plasma concentrations of ganciclovir. However, superposition suggested that i.v. administration of ganciclovir at 2.5 mg/kg every 8 h for 24 h followed by maintenance dosing of 2.5 mg/kg every 12 h would maintain effective ganciclovir serum concentrations in most horses throughout the dosing interval.  相似文献   

12.
Medication control and doping control have been established in horse racing to ensure the integrity of the sport and the welfare of the horses. This ensures that horses do not compete under the influence of any drugs, including omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome. In this study, pharmacokinetic data were produced in equine plasma and urine following an oral administration of 4 mg/kg of generic buffered formulation of omeprazole to six Thoroughbred horses in five daily doses to determine an appropriate screening limit and detection time in equine plasma and to assess whether the current detection time of 72 hr in equine urine would be applicable when an alternative omeprazole product is administered. C max of 436–2,432 ng/ml and AUC 0–tau of 1,476–4,371 ng hr ml?1 were obtained for plasma and indicated, in conjunction with other published oral omeprazole studies, that an appropriate plasma screening limit would be 500 pg/ml with a detection time of 48 hr. Urine analysis showed that omeprazole could be detected for up to 25 hr above the previously established urine screening limit of 500 pg/ml and thus indicated that the detection time advice could be potentially reduced from 72 to 48 hr to allow more comprehensive treatment of gastric lesions.  相似文献   

13.
The present study evaluated the effects of two different methods of feed processing on growth and gastric ulceration in 16 weanling Standardbred horses. The two diets were composed of identical ingredients that were processed differently and fed at a rate of 3% body weight per day. The hay and grain diet (diet HG) consisted of 50% alfalfa hay cubes and 50% commercial texturized grain mix fed as is, without any further processing, with the cubes and grain fed in separate containers. The complete pelleted diet (diet CP) consisted of the same proportion of hay cubes and grain mix, which was ground, pelleted, and fed in a single container. The horses were divided into two groups and the study was divided into three periods of 30 days each. During period 1, all 16 horses consumed only free choice alfalfa hay (diet H). Group 1 was given diet CP during period 2 and diet HG during period 3. Group 2 was given diet HG during period 2 and diet CP during period 3. The horses were endoscopically examined for the baseline number and severity of stomach ulcers at the end of period 1, then again at the end of each treatment diet feeding period. Horses on diet CP in periods 2 and 3 had greater ulcer numbers (P = .0135) than diet HG. However, there was no significant difference (P = .30) in ulcer numbers when making a direct comparison between diets CP and HG. Despite the gastric ulceration found in horses on diet CP, the average daily gain was significantly greater (P = .016) for diet CP than for diet HG. Both diets containing grain were observed to cause gastric ulceration.  相似文献   

14.
The aim of this study was to examine the effects of various levels of supplemental calcium iodate (CI) on productive performance, egg quality, blood indices and iodine (I) accumulation in the eggs in commercial laying hens. A total of 240 White Leghorn layers (Hy‐line W36) were divided through a completely randomized design into six treatments with five replicates and eight hens per each at 32 weeks of age. This experiment lasted for 12 weeks. Concentrations of I in the mash diets were 0.74, 3.13, 5.57, 8.11, 10.65 and 12.94 mg I/kg of feed in treatments 1–6 respectively. The added doses of CI were included 0.0 (control), 2.5, 5.0, 7.5, 10.0 and 12.5 mg/kg of diet for treatments 1–6 respectively. There were no significant differences in productive performance among the treatments. The highest eggshell strength was observed in group fed diet containing 3.13 mg I/kg (p = .014). The highest percentage of calcium and lowest percentage of phosphorus in eggshell were observed in group fed diet containing 12.94 mg I/kg (p = .0001). Feeding hens with diet containing 12.94 mg I/kg increased serum triiodothyronine‐to‐thyroxine ratio (p = .0001). Serum alanine aminotransferase activity in hens fed diet containing 12.94 mg I/kg was significantly more than control (p = .041). Blood Serum triglycerides in hens fed diet containing 8.11 mg I/kg were significantly higher than control (p = .0001). Edible fraction of the eggs of birds fed diet containing 12.94 mg I/kg was enriched by I almost 3 times more than those fed diet containing 0.74 mg I/kg. The results suggested that egg production, egg mass, feed intake and feed conversion ratio were not significantly affected by dietary I levels. Iodine accumulation in the eggs were increased by increasing dietary I levels and the level of 10 mg/kg CI could supply I enrichment of the eggs.  相似文献   

15.
The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher Cmax, shorter Tmax, and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE2 was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC50 of approximately 27 ng/mL and an IC80 of 108 ng/ mL for COX2 inhibition. Inhibition of TXB2 production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.  相似文献   

16.
Flunixin meglumine (FM) is a commonly used Nonsteroidal anti‐inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti‐inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)‐induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS‐induced Thromboxane B2 (TXB2) and Prostaglandin E2 (PGE2) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS‐induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti‐inflammatory and analgesic effects of KT is warranted.  相似文献   

17.
Britzi, M., Gross, M., Lavy, E., Soback, S., Steinman, A. Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses. J. vet. Pharmacol. Therap. 33 , 511–514. Metronidazole (1‐[2‐hydroxyethyl]‐2‐methyl‐5‐nitroimidazole) is a bactericidal antimicrobial agent used for treatment of infectious diseases caused by anaerobic bacteria and protozoa. Pharmacokinetics of metronidazole following its administration to horses was previously described ( Sweeney et al., 1986 ; Baggot et al., 1988 ; Specht et al., 1992 ; Steinman et al., 2000 ). The bioavailability (F) was 85% (ranging from 57% to 105%) and the time to reach maximum serum concentration (tmax) was 1–2 h after oral dose at 25 mg/kg body weight ( Sweeney et al., 1986 ). Baggot et al. (1988) found that F was 74.5% (ranging from 58.4% to 91.5%) and tmax was 1.5 h after oral dose at 20 mg/kg body weight. Specht et al. (1992) reported that F was 97% (ranging from 79% to 111%) and tmax was 40 min after oral dose at 15 mg/kg body weight. In an earlier study by our group F was 74% and tmax was 65 min after oral dose at 20 mg/kg body weight ( Steinman et al., 2000 ). These individual variations in F might be partially explained by the effect of feed, among other factors, mainly on metronidazole absorption. Interactions between food and drugs may reduce or increase the drug effect. The majority of clinically relevant food–drug interactions are caused by food‐induced changes on the bioavailability of the drug ( Schmidt & Dalhoff, 2002 ). In dogs, absorption of metronidazole is enhanced when given with food, but delayed in humans ( Plumb, 1995 ). Although, metronidazole is used commonly to treat various clinical conditions in horses with relatively little adverse effects ( Sweeney et al., 1991 ), narrow margin of safety was suggested because histological evidence of peripheral neurotoxicity and hepatotoxicity were noted in horses treated with doses as low as 30 mg/kg body weight every 12 h orally for 30 days ( White et al., 1996 ). For drugs with a narrow therapeutic index, even small changes in dose–response effects can have significant consequences ( Schmidt & Dalhoff, 2002 ).  相似文献   

18.
The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5 mg/kg morphine. Blood samples were collected up to 72 h postdrug administration, analyzed using LC‐MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half‐life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1 h, respectively, following administration of the four different IV doses. The volume of distribution at steady‐state and systemic clearance ranged from 6.95 to 15.8 L/kg and 28.3 to 35.7 mL·min/kg, respectively. The only metabolites identified in blood samples were the primary metabolites identified in other species, 3‐morphine‐glucuronide and 6‐morphine‐glucuronide. Muscle fasciculations were observed at 0.2 and 0.5 mg/kg and ataxia noted at 0.5 mg/kg. Gastrointestinal activity was decreased in all dose groups (for up to 8 h in 7/8 horses and 24 h in one horse). This study extends previous studies and is the first report describing the metabolites of morphine in the horse. Plasma concentrations of morphine‐3‐glucuronide, a metabolite with demonstrated neuro‐excitatory activity in mice, far exceeded that of morphine‐6‐glucuronide. Further study is warranted to assess whether the high levels of the morphine‐3‐glucuronide contribute to the dose‐dependent excitation observed at high morphine doses.  相似文献   

19.
Dietary capsaicin enhances disease resistance and immunity in various species. Because relatively little is known about the potential benefits of capsaicin when used on horses, this study was conducted to determine the effect of dietary capsaicin on measures of health in horses. Twelve horses were fed over 28 days a basal diet with three levels of dietary capsaicin: 0 mg (C), 50 mg (CAP50), or 100 mg (CAP100) per horse per day. Before feeding on day 0, horses were weighed, a blood sample taken, and a sample of synovial fluid from the left distal carpal joint was taken. Subsequent body weights and blood samples were obtained on days 7, 14, 21, and 28. On day 21, tetanus toxoid (TT) and an immunomodulator (EqStim) were given to each horse. On days 21 to 28, daily rectal temperature (RT) and blood samples were taken. On day 28, synovial fluid was obtained immediately after blood sampling and RT measurement. Synovial concentrations of prostaglandin E2 did not differ among dietary treatments or between days 0 and 28. No effect of dietary capsaicin on serum immunoglobulin G subclass T or α1-acid glycoprotein concentrations was observed. Serum haptoglobin was elevated (P < .0003) and RT increased (P < .05) after challenge with EqStim and TT; however, haptoglobin concentrations and RT did not differ due to diet. We conclude that the doses of dietary capsaicin fed to horses in this study had no beneficial effect on measures of joint health or the immune response in horses.  相似文献   

20.
The disposition of plasma glycopyrrolate (GLY) is characterized by a three‐compartment pharmacokinetic model after a 1‐mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V1), volume of distribution at steady‐state (Vss), and area under the plasma concentration–time curve (AUC0‐inf) were 16.7 (13.6–21.7) mL/min/kg, 0.167 (0.103–0.215) L/kg, 3.69 (0.640–38.73) L/kg, and 2.58 (2.28–2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92–3.59) mL/min/kg and represented approximately 11.3–24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses.  相似文献   

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